The hypoxia‐inducible factor is stabilized in circulating hematopoietic stem cells under normoxic conditions

The hypoxia‐inducible factor (HIF) transcriptional system enables cell adaptation to limited O2 availability, transducing this signal into patho‐physiological responses such as angiogenesis, erythropoiesis, vasomotor control, and altered energy metabolism, as well as cell survival decisions. However, other factors beyond hypoxia are known to activate this pleiotropic transcription factor. The aim of this study was to characterize HIF in human hematopoietic stem cells (HSCs) and evidence is provided that granulocyte colony stimulating factor‐mobilized CD34+‐ and CD133+‐HSCs express a stabilized cytoplasmic form of HIF‐1α under normoxic conditions. It is shown that HIF‐1α stabilization correlates with down‐regulation of the tumour suppressor von Hippel‐Lindau protein (pVHL) and is positively controlled by NADPH‐oxidase‐dependent production of reactive oxygen species, indicating a specific O2‐independent post‐transcriptional control of HIF in mobilized HSCs. This novel finding is discussed in the context of the proposed role of HIF as a mediator of progenitor cell recruitment to injured ischemic tissues and/or in the control of the maintenance of the undifferentiated state.

• Publication year

  2007

• Venue

  FEBS Letters

• Publication date

  2007-06-26

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.febslet.2007.05.077PMID 17568584
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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